Holly J. Ramsawh

Relationship of anxiety disorders, sleep quality, and functional impairment in a community sample

BACKGROUND Anxiety disorders and insomnia are each prevalent, impairing, and highly comorbid. However, little is known about whether specific types of sleep complaints are associated with specific anxiety disorders, and whether poor sleep has an additive effect on functional impairment in anxiety disorders. METHOD Data from the German Health Survey (GHS; N = 4181; ages 18-65) were utilized to examine relationships among anxiety disorders, sleep quality (assessed by the Pittsburgh Sleep Quality Inventory; PSQI), and functional impairment (assessed by the Medical Outcomes Scale Short Form; SF-36; and past-month disability days due to physical and emotional problems, respectively). RESULTS Most anxiety disorders were significantly associated with global PSQI scores. Social phobia (AOR 3.95, 95% CI 1.73-9.04) and GAD (AOR 3.94, 95% CI 1.66-9.34) had the strongest relationships with global PSQI scores. Daytime dysfunction was the PSQI subscale most strongly associated with anxiety disorders, particularly GAD. Having a comorbid anxiety disorder and poor sleep was associated with significantly lower Mental Component Scores on the SF-36 than having an anxiety disorder alone (40.87 versus 43.87, p = .011) and with increased odds of one or more disability days due to emotional problems (AOR 2.72, 95% CI 1.35-5.48), even after controlling for sociodemographic factors and past-month mood and substance use disorders. CONCLUSIONS Most anxiety disorders are moderately associated with reduced sleep quality. Individuals with anxiety disorders and poor sleep experience significantly worse mental health-related quality of life and increased disability relative to those with anxiety disorders alone.

Prefrontal dysfunction during emotion regulation in generalized anxiety and panic disorders

BACKGROUND The mechanisms that contribute to emotion dysregulation in anxiety disorders are not well understood. Two common disorders, generalized anxiety disorder (GAD) and panic disorder (PD), were examined to test the hypothesis that both disorders are characterized by hypo-activation in prefrontal cortex (PFC) during emotion regulation. A competing hypothesis that GAD in particular is characterized by PFC hyper-activation during emotion regulation (reflecting overactive top-down control) was also evaluated. Method Twenty-two medication-free healthy control (HC), 23 GAD, and 18 PD participants underwent functional magnetic resonance imaging (fMRI) during a task that required them to reappraise (i.e. reduce) or maintain emotional responses to negative images. RESULTS GAD participants reported the least reappraisal use in daily life, and reappraisal use was inversely associated with anxiety severity and functional impairment in these participants. During fMRI, HCs demonstrated greater activation during both reappraisal and maintenance than either GAD or PD participants (who did not differ) in brain areas important for emotion regulation (e.g. dorsolateral and dorsomedial PFC). Furthermore, across all anxious participants, activation during reappraisal in dorsolateral and dorsomedial PFC was inversely associated with anxiety severity and functional impairment. CONCLUSIONS Emotion dysregulation in GAD and PD may be the consequence of PFC hypo-activation during emotion regulation, consistent with insufficient top-down control. The relationship between PFC hypo-activation and functional impairment suggests that the failure to engage PFC during emotion regulation may be part of the critical transition from dispositionally high anxiety to an anxiety disorder.

Risk for suicidal behaviors associated with PTSD, depression,and their comorbidity in the U.S. Army

BACKGROUND Suicide rates have risen considerably in the United States Army in the past decade. Suicide risk is highest among those with past suicidality (suicidal ideation or attempts). The incidence of posttraumatic stress disorder (PTSD) and depressive illnesses has risen concurrently in the U.S. Army. We examined the relationship of PTSD and depression, independently and in combination, and rates of past-year suicidality in a representative sample of U.S. Army soldiers. METHODS This study used the DoD Survey of Health Related Behaviors Among Active Duty Military Personnel (DoD HRB) (N=5927). Probable PTSD and depression were assessed with the PTSD Checklist (PCL) and the 10-item short form of the Center for Epidemiologic Studies Depression Scale (CES-D), respectively. Past-year suicidality was assessed via self-report. RESULTS Six percent of Army service members reported suicidality within the past year. PTSD and MDD were each independently associated with past-year suicidality. Soldiers with both disorders were almost three times more likely to report suicidality within the past year than those with either diagnosis alone. Population-attributable risk proportions for PTSD, depression, and both disorders together were 24%, 29%, and 45%, respectively. LIMITATIONS The current study is subject to the limitations of a cross-sectional survey design and the self-report nature of the instruments used. CONCLUSIONS PTSD and depression are each associated with suicidality independently and in combination in the active duty component of the U.S. Army. Soldiers presenting with either but especially both disorders may require additional outreach and screening to decrease suicidal ideation and attempts.

Age of onset, clinical characteristics, and 15-year course of anxiety disorders in a prospective, longitudinal, observational study.

BACKGROUND Age of onset is rarely studied in the anxiety disorders literature. The current study examined age of onset as it relates to clinical characteristics and course of anxiety disorders using a prospective, longitudinal, observational design. METHODS Fifteen-year follow-up data were examined for participants with panic disorder with (PDA) or without (PD) agoraphobia, social phobia (SP), and/or generalized anxiety disorder (GAD) at baseline. Logistic regression analyses were conducted to determine whether age of onset was associated with demographic or clinical variables at baseline. Cox regression analyses were conducted to examine longitudinal course (time to recurrence and recovery, respectively) for each diagnostic group. RESULTS At baseline, PD participants with early onset (i.e., < age 20) were more likely to have comorbid MDD, GAD, and SP relative to late-onset participants (≥ age 20). For PDA, early-onset participants were less likely to be married, and more likely to have both GAD and SP at baseline. With respect to longitudinal course, earlier onset was associated with an increased likelihood of recurrence in participants with PDA. No other models reached significance. LIMITATIONS The sample sizes for some disorders were comparatively small in relation to PDA, and all participants were treatment-seeking, which may limit generalizability. CONCLUSIONS For some anxiety disorders, earlier age of onset appears to be associated with greater severity and worse course, as evidenced by increased risk of recurrence over 15years of follow-up. Early interventions focused on children and adolescents may alleviate some of the public health burden associated with anxiety disorders.

Single-Subject Anxiety Treatment Outcome Prediction using Functional Neuroimaging

The possibility of individualized treatment prediction has profound implications for the development of personalized interventions for patients with anxiety disorders. Here we utilize random forest classification and pre-treatment functional magnetic resonance imaging (fMRI) data from individuals with generalized anxiety disorder (GAD) and panic disorder (PD) to generate individual subject treatment outcome predictions. Before cognitive behavioral therapy (CBT), 48 adults (25 GAD and 23 PD) reduced (via cognitive reappraisal) or maintained their emotional responses to negative images during fMRI scanning. CBT responder status was predicted using activations from 70 anatomically defined regions. The final random forest model included 10 predictors contributing most to classification accuracy. A similar analysis was conducted using the clinical and demographic variables. Activations in the hippocampus during maintenance and anterior insula, superior temporal, supramarginal, and superior frontal gyri during reappraisal were among the best predictors, with greater activation in responders than non-responders. The final fMRI-based model yielded 79% accuracy, with good sensitivity (0.86), specificity (0.68), and positive and negative likelihood ratios (2.73, 0.20). Clinical and demographic variables yielded poorer accuracy (69%), sensitivity (0.79), specificity (0.53), and likelihood ratios (1.67, 0.39). This is the first use of random forest models to predict treatment outcome from pre-treatment neuroimaging data in psychiatry. Together, random forest models and fMRI can provide single-subject predictions with good test characteristics. Moreover, activation patterns are consistent with the notion that greater activation in cortico-limbic circuitry predicts better CBT response in GAD and PD.

Anxiety in middle adulthood: effects of age and time on the 14-year course of panic disorder, social phobia and generalized anxiety disorder

BACKGROUND Much about the long-term course of anxiety disorders is unknown. The present study utilizes a naturalistic, longitudinal, short-interval follow-up design to elucidate the course of anxiety disorders over 14 years in a largely middle-aged adult sample recruited from out-patient psychiatry and primary care facilities. METHOD The sample consisted of 453 participants with a diagnosis of panic disorder (PD), social phobia (SP) and/or generalized anxiety disorder (GAD). Anxiety symptom ratings were tracked using weekly psychiatric status ratings (PSRs). Controlling for demographic and clinical variables, the course of PD, GAD and SP were examined using longitudinal growth models, with the most severe PSR at each follow-up point as the main outcome variable. RESULTS PSRs significantly decreased in severity over time in each of the three disorders. In the interaction effects models, age x time had a significant effect on course for PD and GAD, but not for SP, in that older age was associated with lower PSRs over time. CONCLUSIONS The present findings suggest that the severity of anxiety disorders declines over time, although this decline is modest and depends on the specific disorder being assessed. Older individuals with PD and GAD have a better prognosis than their younger counterparts, as their course is characterized by a steeper decline in severity. The present findings provide important information about the course of anxiety disorders in mid-life.

Anxiety sensitivity as a predictor of the clinical course of panic disorder: a 1‐year follow‐up study

Background: There is evidence that negative affect (NA) and anxiety sensitivity (AS) predict the development of anxiety disorders, particularly panic disorder (PD). The main purpose of this study was to examine whether NA and AS will also predict the clinical course of PD. Methods: Participants were 136 individuals with a DSM‐III‐R diagnosis of PD (with or without agoraphobia) enrolled in a naturalistic and longitudinal study of anxiety disorders, the Harvard/Brown Anxiety Research Project (HARP). Participants were administered the Anxiety Sensitivity Index and the Negative Affect Scales of the Positive and Negative Affect Schedule‐Expanded Form (PANAS‐X‐NA) and their percentage of time in PD episode was followed for 1 year after the administration of the measures. Results: Multiple regression analyses indicated that AS, but not NA, was a significant predictor of percentage of time in PD episode after controlling for previous time in PD episodes, comorbid depression, other anxiety disorders, and exposure to psychopharmacological and behavioral treatments. As expected, the Physical Concerns subscale of the Anxiety Sensitivity Index had a significant independent contribution in predicting the course of the disorder. Conclusions: Overall, these findings suggest that AS, as a unique construct, may be predictive of the amount of time patients are in episode of PD. Depression and Anxiety, 2009. Published 2009 Wiley‐Liss, Inc.

Burden of anxiety disorders in pediatric medical settings: prevalence, phenomenology, and a research agenda

The current review describes the phenomenology of several common anxiety disorders in children and adolescents as they present in medical settings. Anxiety disorders and associated features in children are described, along with epidemiology, functional impairment, common somatic complaints, medical comorbidity, health care utilization, and presentation in general and in specialty pediatric medical settings. Recommendations for clinical management in pediatric settings are presented, and evidence-based interventions and emerging treatments for pediatric anxiety disorders are described. The review concludes with a discussion of future research directions that may lead to increased recognition and improved management of anxiety disorders in pediatric medical settings.

Common and disorder-specific neural responses to emotional faces in generalised anxiety, social anxiety and panic disorders.

BACKGROUND Although evidence exists for abnormal brain function across various anxiety disorders, direct comparison of neural function across diagnoses is needed to elicit abnormalities common across disorders and those distinct to a particular diagnosis. AIMS To delineate common and distinct abnormalities within generalised anxiety (GAD), panic and social anxiety disorder (SAD) during affective processing. METHOD Fifty-nine adults (15 with GAD, 15 with panic disorder, 14 with SAD, and 15 healthy controls) underwent functional magnetic resonance imaging while completing a facial emotion matching task with fearful, angry and happy faces. RESULTS Greater differential right amygdala activation to matching fearful v. happy facial expressions related to greater negative affectivity (i.e. trait anxiety) and was heightened across all anxiety disorder groups compared with controls. Collapsing across emotional face types, participants with panic disorder uniquely displayed greater posterior insula activation. CONCLUSIONS These preliminary results highlight a common neural basis for clinical anxiety in these diagnoses and also suggest the presence of disorder-specific dysfunction.

Cognitive-Behavioral Therapy for Generalized Anxiety Disorder is Associated with Attenuation of Limbic Activation to Threat-Related Facial Emotions

BACKGROUND The neural processes underlying the benefits of cognitive behavioral treatment (CBT) for generalized anxiety disorder (GAD) are not well understood. METHODS Twenty-one (n=21) adults with a principal diagnosis of GAD and eleven (n=11) non-anxious healthy controls (HC) underwent functional magnetic resonance imaging while completing a facial emotion processing task. Responses to threat-related emotionality (i.e., the contrast of fear and angry vs. happy faces) were assessed at pretreatment and again following 10 sessions of CBT in the GAD group and a comparable waiting period in the HC group. RESULTS At pretreatment, GAD participants displayed blunted responses in the amygdala, insula, and anterior cingulate to the happy face-processing comparison condition, and greater amygdalo-insular connectivity. CBT was associated with attenuated amygdalar and subgenual anterior cingulate activation to fear/angry faces and heightened insular responses to the happy face comparison condition, but had no apparent effects on connectivity. Pre-treatment abnormalities and treatment-related changes were not associated with symptoms of worry. LIMITATIONS There was no active control condition (e.g., treatment waitlist) for comparison of treatment effects. CONCLUSIONS Taken together, these results provide evidence for a dual-process psychotherapeutic model of neural systems changes in GAD in which cingulo-amygdalar reactivity to threat-cues is attenuated while insular responses to positive facial emotions are potentiated. Future work is needed to determine the clinical implications of these changes and their specificity to CBT.